Titre :

Path to clonal theranostics in luminal breast cancers

Auteur(s) :

Hajjaji, Nawale [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Aboulouard, Soulaimane [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Cardon, Tristan [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Bertin, Delphine [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Robin, Yves-Marie [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
FOURNIER, Isabelle [Auteur]
Institut universitaire de France [IUF]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Salzet, Michel [Auteur]
Institut universitaire de France [IUF]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Titre de la revue :

Frontiers in Oncology

Nom court de la revue :

Front Oncol

Numéro :

11

Pagination :

802177

Éditeur :

Frontiers

Date de publication :

2022-01-13

ISSN :

2234-943X

Mot(s)-clé(s) en anglais :

mutated and alternative proteomes
functional tumor heterogeneity
spatially resolved MALDI mass spectrometry imaging
drug repurposing and drug target discovery
microproteomics
spatially resolved proteome
luminal breast cancers
clonal theranostics

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Integrating tumor heterogeneity in the drug discovery process is a key challenge to tackle breast cancer resistance. Identifying protein targets for functionally distinct tumor clones is particularly important to tailor ...
Lire la suite >Integrating tumor heterogeneity in the drug discovery process is a key challenge to tackle breast cancer resistance. Identifying protein targets for functionally distinct tumor clones is particularly important to tailor therapy to the heterogeneous tumor subpopulations and achieve clonal theranostics. For this purpose, we performed an unsupervised, label-free, spatially resolved shotgun proteomics guided by MALDI mass spectrometry imaging (MSI) on 124 selected tumor clonal areas from early luminal breast cancers, tumor stroma, and breast cancer metastases. 2868 proteins were identified. The main protein classes found in the clonal proteome dataset were enzymes, cytoskeletal proteins, membrane-traffic, translational or scaffold proteins, or transporters. As a comparison, gene-specific transcriptional regulators, chromatin related proteins or transmembrane signal receptor were more abundant in the TCGA dataset. Moreover, 26 mutated proteins have been identified. Similarly, expanding the search to alternative proteins databases retrieved 126 alternative proteins in the clonal proteome dataset. Most of these alternative proteins were coded mainly from non-coding RNA. To fully understand the molecular information brought by our approach and its relevance to drug target discovery, the clonal proteomic dataset was further compared to the TCGA breast cancer database and two transcriptomic panels, BC360 (nanoString((R))) and CDx (Foundation One((R))). We retrieved 139 pathways in the clonal proteome dataset. Only 55% of these pathways were also present in the TCGA dataset, 68% in BC360 and 50% in CDx. Seven of these pathways have been suggested as candidate for drug targeting, 22 have been associated with breast cancer in experimental or clinical reports, the remaining 19 pathways have been understudied in breast cancer. Among the anticancer drugs, 35 drugs matched uniquely with the clonal proteome dataset, with only 7 of them already approved in breast cancer. The number of target and drug interactions with non-anticancer drugs (such as agents targeting the cardiovascular system, metabolism, the musculoskeletal or the nervous systems) was higher in the clonal proteome dataset (540 interactions) compared to TCGA (83 interactions), BC360 (419 interactions), or CDx (172 interactions). Many of the protein targets identified and drugs screened were clinically relevant to breast cancer and are in clinical trials. Thus, we described the non-redundant knowledge brought by this clone-tailored approach compared to TCGA or transcriptomic panels, the targetable proteins identified in the clonal proteome dataset, and the potential of this approach for drug discovery and repurposing through drug interactions with antineoplastic agents and non-anticancer drugs.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

INSERM
Université de Lille

Collections :

• Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Date de dépôt :

2022-06-15T14:00:46Z
2023-03-09T18:01:11Z